There are numerous automatic clinical analysis type instruments available on the market today. Typical of these is the Automatic Clinical Analyzer known as the aca.RTM. sold by E. I. du Pont de Nemours & Co., Inc. This is an instrument in which the incubator is a belt or chain in which a sample, associated with reagent packs, is analyzed for its various components. While quite satisfactory for many purposes it does not have the versatility required for some of the more recently developed immunoassay type tasks. Other machines that are available are those that are described, for example, in U.S. Pat. No. 4,315,891 assigned to Olympus Optical Company. This patent also deals with a belt or chain incubator instrument and has a single reaction line in which reaction vessels are carried step by step along the reaction line. Samples and reagents are delivered to the vessels during their movement along the reaction line to obtain a test liquid which is then subjected to photometric analysis. This machine permits several tests to be run simultaneously on samples by an interleaving processing. Unfortunately, this apparatus does not have the capability for performing the precise washing required in heterogeneous immunoassays. Another automatic analytical apparatus is that described in U.S. Pat. No. 4,459,265 assigned to Clinicon. This apparatus includes a stepwise rotatable circular plate. It carries a plurality of reaction tubes on its periphery with several reagent supply stations arranged at different locations around such periphery. The use of multiple stations does provide the machine with the versatility to carry out several different test methodologies, but again does not provide the necessary washing required for heterogeneous immunoassays.
Such heterogeneous immunoassays typically are performed using a solid support, preferably with the solid support being formed from magnetic particles. A particularly preferred support for this purpose is that described in U.S. Pat. No. 4,661,408 assigned to E. I. du Pont de Nemours & Co., Inc. This patent describes a chromium dioxide particle which has favorable magnetic properties for use as a solid support in such assays.
The concept of using magnetically responsive particles to effect separations of bioactive materials is old in the art (Hedin, C. G., Biotech. Bioeng. Symp. No. 3 (1972) 173-174; Robinson, P. J., et al., Biotech Bioeng. (1973) 15, 603-606). The concept has been extended over time to include affinity purification of enzymes, proteins or microorganisms applicable to any sorption-desorption process (Dunhill, P., et al., Biotech. Bioeng. (1974) 10,987-990; Horisberger, M., Biotech. Bioeng. (1976) 18, 1647-1651).
Another improved magnetically responsive particle is described by Mansfield et al. in U.S. Pat. No. 4,197,337. These particles are porous glass microparticles with magnetic material imbedded within them. This gives the particles the properties of high surface area, inertness and being substantially superparamagnetic. This high surface area again favors rapid reaction kinetics and increases capacity of the individual particles. Being substantially superparamagnetic, basically means the particles do not retain much magnetic memory, or retentitivity, when removed from a magnetic field. This means that particles can be repeatedly separated from their environment by a magnetic field without affecting the ability to redisperse those particles. This is of advantage in sandwich immunoassays where multiple washing steps may require repeated separation and redispersion.
The protected CrO.sub.2 particles described in the Du Pont patent have several properties that are particularly advantageous in heterogeneous immunoassays. These are:
low remanent magnetism and favorable surface structure--allowing repeated magnetic separation/dispersion cycles; PA1 rapid separation in a magnetic field; PA1 high surface area for high capture capacity; PA1 a highly stable particle for maximum reagent shelf life.
One problem with immunoassays is that they require repeated washing of the solid support containing the bound component following removal of the free component. This is a particularly difficult procedure even when performed manually. It is a particular problem when the automatic wash procedure is incorporated into an automatic instrument which is capable of performing immunoassays. The typical requirements for purity in such immunoassays is that the bound component remaining following such washes should not contain more than 20 parts per million of the original sample/conjugate matrix. This necessitates the use of multiple wash stations and can be accomplished in automatic instruments by providing such multiple wash stations. However, the several mechanisms required to operate individually the several wash stations and the mechanisms required for the wash stations themselves can become quite expensive.
It is known in a conventional chemical analyzer an instrument produced by Hitachi, Inc., Tokyo, Japan, Model Number 7050 to link together or "gang" plural wash probes. When this is accomplished, however, the ability of the instrument to perform multiple analytical procedures at the same time or operation is severly impaired.